Medial frontal ∼4-Hz activity in humans and rodents is attenuated in PD patients and in rodents with cortical dopamine depletion
Medial frontal ∼4-Hz activity in humans and rodents is attenuated in PD patients and in rodents with cortical dopamine depletion
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DOI：
10.1152/jn.00412.2015
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发表时间：
2015-08-01
影响因子：
2.5
通讯作者：
Narayanan, Nandakumar S.
中科院分区：
文献类型：
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作者：
Parker, Krystal L.;Chen, Kuan-Hua;Narayanan, Nandakumar S.
动作的时间控制是哺乳动物的一种高度保守和关键的行为。在这里，我们使用间隔计时任务来研究这一过程的神经元基础。在大鼠和人类中，指导性定时线索从内侧额叶皮质(MFC)触发了跨Delta和Theta频段(2-6赫兹)的频谱功率。我们发现，患有帕金森氏病(PD)的人和患有局部MFC多巴胺缺乏的啮齿动物都减弱了Delta和theta的活动。在啮齿动物中，在这个范围内的光谱活动可以在功能上耦合参与时间处理的单个MFC神经元。没有MFC多巴胺，这些神经元与Delta/theta活动的功能耦合较少，时间处理也较少。最后，在人类中，这种2至6赫兹的活动与执行功能相关，在匹配的对照组中，但在帕金森病患者中没有。总之，这些发现表明，提示诱发的低频节律可能是临床上重要的帕金森病生物标记物，可翻译成啮齿动物模型，促进机制研究和人类疾病神经生理学生物标记物的发展。
The temporal control of action is a highly conserved and critical mammalian behavior. Here, we investigate the neuronal basis of this process using an interval timing task. In rats and humans, instructional timing cues triggered spectral power across delta and theta bands (2-6 Hz) from the medial frontal cortex (MFC). Humans and rodents with dysfunctional dopamine have impaired interval timing, and we found that both humans with Parkinson's disease (PD) and rodents with local MFC dopamine depletion had attenuated delta and theta activity. In rodents, spectral activity in this range could functionally couple single MFC neurons involved in temporal processing. Without MFC dopamine, these neurons had less functional coupling with delta/theta activity and less temporal processing. Finally, in humans this 2- to 6-Hz activity was correlated with executive function in matched controls but not in PD patients. Collectively, these findings suggest that cue-evoked low-frequency rhythms could be a clinically important biomarker of PD that is translatable to rodent models, facilitating mechanistic inquiry and the development of neurophysiological biomarkers for human disease.